title: Lack of ADAM10 in endothelial cells affects osteoclasts at the chondro-osseus junction.
abstract: Mice lacking ADAM10 in endothelial cells (Adam10ΔEC mice) have shorter femurs, tibiae, and humeri than controls, raising questions about how endothelial cells could control long bone growth. We performed a histopathological evaluation of the femur and tibia growth plates at different postnatal stages, and assessed the distribution of TRAP-positive osteoclasts and endothelial cells at the growth plate. The growth plates in Adam10ΔEC mice appeared normal at P7 and P14, but a thickened zone of hypertrophic chondrocytes and increased trabecular bone density were apparent by P21 and later. The number of TRAP+ cells at the COJ was normal at P7 and P14, but was strongly reduced at P21 and later. Moreover, the density of endomucin-stained endothelial cells at the COJ was increased starting at P7. The defects in long bone growth in Adam10ΔEC mice could be caused by a lack of osteoclastogenesis at the COJ. Moreover, ADAM10 appears to regulate endothelial cell organization in the developing bone vasculature, perhaps in a similar manner as in the developing retinal vascular tree, where ADAM10 is thought to control Notch-dependent endothelial cell fate decisions. This study provides evidence for the regulation of osteoclast function by endothelial cells in vivo.
authors.affiliation: Department of Orthopedics, Daping Hospital, Third Military Medical University, Chongqing, 400042, P.R. China; Arthritis and Tissue Degeneration Program, New York, New York, 10021.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhao
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Hall
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.forename: Gisela
authors.initials: G
authors.lastname: Weskamp
authors.forename: Baohong
authors.initials: B
authors.lastname: Zhao
authors.forename: Daniel
authors.initials: D
authors.lastname: Hill
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Glomski
authors.forename: Carl P
authors.initials: CP
authors.lastname: Blobel
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000072197:ADAM10 Protein; D000135:Acid Phosphatase / Q000378:metabolism; D000375:Aging; D053829:Amyloid Precursor Protein Secretases / Q000172:deficiency*; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D005269:Femur / Q000098:blood supply / Q000254:growth & development; D006132:Growth Plate / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D010010:Osteoclasts / Q000502:physiology*; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000254:growth & development
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse
keywords: ADAM10; chondro-osseus junction; endothelial cells; growth plate; osteoclasts